Chimeric antigen receptor T-cell (CAR T-cell) therapy is a type of immunotherapy in which a person’s T-cells are engineered in the laboratory so that they can fight against cancer cells.
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New drugs that harness the body’s immune system to destroy cancer cells appear to increase the effectiveness of later drug therapies for non-Hodgkin and Hodgkin lymphoma patients, new research suggests. This happens, scientists say, even for repeat drug therapies whose initial attempts failed to stop or reverse the disease.
Researchers at NYU School of Medicine and ٺƵ’s Perlmutter Cancer Center who led the pair of new studies presented the findings on December 1 at the annual meeting of the American Society of Hematology in San Diego. The findings are the first multicenter data to show that even when “second-line” immunotherapy fails to control the disease, it likely “sensitizes” lymphoma patients to better respond to future use of medications that did not work very well the first time. Few treatment options exist, researchers say, for patients with relapsing non-Hodgkin lymphoma.
Both studies involved a review of the medical records of men and women treated between 2012 and 2018 at 17 medical centers in the United States and Canada, all of whom failed to have a lasting response to initial therapy, including stem cell transplantations and/or standard chemotherapy with or without brentuximab vedotin (marketed as Adcetris®), a drug that primes the immune system and aids chemotherapy.
Subsequent therapy with so-called checkpoint-blockade inhibitors, such as ipilimumab (Yervoy®) and nivolumab (Opdivo®), were also not successful in controlling cancer spread. When effective, such drugs work by turning off inhibitory switches, or “checkpoints,” on immune T cell surfaces, which are known to prevent the immune system from identifying and attacking tumor cells.
However, in 59 patients with non-Hodgkin lymphoma, 30 responded to additional chemotherapy or other drug treatment after having received checkpoint inhibitors. Of the 29 patients still alive and receiving therapy, 16 have not seen any cancer spread.
In 112 patients with Hodgkin lymphoma who received checkpoint blockade therapy, 81 needed some form of follow-up drug treatment. Sixty-six remain alive, and 30 have not experienced any worsening of their disease.
“These are very high success rates for post-checkpoint blockade therapy, especially in patients for whom several drug therapies have failed, including the same or similar drugs used again after checkpoint therapy,” says senior study investigator and hematologist-oncologist Catherine S. Diefenbach, MD.
Diefenbach, an assistant professor at ٺƵ and clinical director of lymphoma program services at Perlmutter Cancer Center, cautioned that prospective clinical trials, in which patients are closely monitored from the start of their therapy over long periods of time, are needed before researchers can conclude whether or not checkpoint blockade therapy was responsible for the greater effectiveness of subsequent treatments.
“What our current study strongly suggests, however, is that the benefits of checkpoint blockade therapy are not limited to their initial ability to stop the disease,” says lead study investigator Nicole Carreau, MD, a postdoctoral hematology and oncology fellow at ٺƵ and Perlmutter Cancer Center.
Both kinds of lymphoma are cancers of immune cells that help the body fight off infections and other diseases, says Carreau. Non-Hodgkin lymphoma is more common in the United States, with more than 72,000 new cases diagnosed each year (with more than 20,000 deaths from the disease), compared with about 8,500 for Hodgkin lymphoma (and more than 1,000 deaths).
Funding support for the study, known formally as the ECOG-ACRIN Cancer Research Group, was provided by National Cancer Institute grants R01 CA180820, R01 CA180794, R01 CA180790, R01 CA180795, U10 CA180799, R01 CA180802, R01 CA180816, R01 CA180833, R01 CA180864, and R01 CA180847. Additional research support was provided to Diefenbach by American Cancer Society grant MRSG-14-052-01.
Diefenbach reports having received consulting fees and research funding from Seattle Genetics and Bristol-Myers Squibb, the manufacturers of the drugs used in this study. She has also received consulting fees and research funding from Bayer; Genentech; Incyte; LAM Therapeutics; MEI; Merck; Millennium; and Roche; and reports a financial interest in Gilead Sciences—companies involved in the production and development of several lymphoma therapies. All relationships are being managed in accordance with the policies of ٺƵ.
Besides Diefenbach and Carreau, other ٺƵ researchers involved in this study are ; Orrin Pail, MD; and Yuhe Xia, MS. Additional study investigators are Philippe Armand, MD, and Reid Merryman, MD, at Dana-Farber Cancer Institute in Boston; Ranjana Advani, MD, and Michael Spinner, MD, at Stanford University in California; Alex Herrera, MD, Robert Chen, MD, and Sarah Tomassetti, MD, at City of Hope National Medical Center in Duarte, California; Radhakrishnan Ramchandren, MD, and Muhammad Hamid, MD, at Wayne State University in Detroit; Sarit Assouline, MD, and Raoul Santiago, MD, at McGill University in Montreal; Nina Wagner-Johnston, MD, and Suman Paul, MD, PhD, at Johns Hopkins Medicine in Baltimore; Jakub Svoboda, MD, and Steven Bair, MD, at Penn Medicine in Philadelphia; Stefan Barta, MD, MS, and Yang Lui, MD, at Fox Chase Cancer Center in Philadelphia; James Godfrey, MD, at University of Chicago; Sunita Nathan, MD, and Reem Karmali, MD, at Rush University in Chicago; Madelyn Burkhart, MD, at Northwestern University in Chicago; Pallawi Torka, MD, at Rosswell Park Cancer Center in Buffalo, New York; Kevin David, MD, and Catherine Wei, MD, at Rutgers Cancer Institute of New Jersey in New Brunswick; Frederick Lansigan, MD, at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire; Daniel Persky, MD, at the University of Arizona in Tucson; Sonali Smith, MD, at University of Chicago Medicine; and Julio Chavez, MD, at the Moffitt Cancer Center in Tampa.
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